The Japanese classification of computed tomography for pneumoconioses with standard films: comparison with the ILO international classification of radiographs for pneumoconioses

Computed tomography (CT) has recently come to be used for personal diagnosis of pneumoconioses and preliminarily for epidemiological purposes. This study aimed to compare the diagnosis of pneumoconioses b y t h e J a p a n e s e C l a s s i f i c a t i o n o f C T f o r Pneumoconioses (Hosoda-Shida Classification) with that by the ILO International Classification of Radiographs of Pneumoconioses (ILO 1980 standard). The Hosoda-Shida Classification is also described in this article. Subjects and Methods: CT and chest posterior-anterior X-ray (CXR) were performed in 21 subjects with an occupational history of mining, and 6 subject without exposure to any risk of pneumoconiosis. Three radiologists independently described the findings of CT and CXR according to both the Hosoda-Shida Classification and the ILO 1980 standard, respectively. Results: At least two of the three readers agreed in determining both the profusion and the type of small rounded opacities in 96% (26/27) of the CT films. The inter-reader agreement of profusion was satisfactory Received May 25, 2000; Accepted Oct 3, 2000 Correspondence to: N. Suganuma, Department of Environmental Health, Fukui Medical University School of Medicine, Fukui 910-1193 with the Cohen's weighted kappa value of 0.57 to 0.71. The weighted kappa for CXR and CT in describing the profusion and the type of small rounded opacities were 0.70 and 0.77, respectively. Conclusion: The HosodaShida Classification for pneumoconioses is shown to be reliable and compatible with the ILO 1980 standard in describing the profusion and the type of small opacities. (J Occup Health 2001; 43: 24-31

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

Chicken ghrelin: purification, cDNA cloning, and biological activity

In this study, we report the purification, cDNA cloning, and characterization of the novel growth hormone-releasing peptide, ghrelin, in the chicken (Gallus gallus). Chicken ghrelin is composed of 26 amino acids (GSSFLSPTYKNIQQQKDTRKPTARLH) and possesses 54% sequence identity with human ghrelin. The serine residue at position 3 (Ser(3)) is conserved between the chicken and mammalian species, as its acylation by either n-octanoic or n-decanoic acid. Chicken ghrelin mRNA is predominantly expressed in the stomach, where it is present in the proventriculus but absent in the gizzard. Using RT-PCR analysis, low levels of expression were also detectable in brain, lung, and intestine. Administration of chicken ghrelin increases plasma GH levels in both rats and chicks, with a potency similar to that of rat or human ghrelin. In addition, chicken ghrelin also increases plasma corticosterone levels in growing chicks at a lower dose than in mammals. The present results indicate that the stimulatory effect of ghrelin on GH secretion is evolutionarily conserved, whereas its effect on adrenal function seems to be unique in the chicken.status: publishe